Our objective in this continuing study has been to identify and produce tumor-localizing radiopharmaceuticals that can be used for the early detection of cancer in humans. We have shown that Ga67 and In111 (and possibly the rare earth radionuclides) have tumor-specific lysosomotropic characteristics with unusual subcellular binding properties in tumor tissue. We propose in this application a renewal of NCI research grant RO1 CA 11858 to extend our present studies to more definitive characterizations of the organelle and macromolecular binding components for these agents which appear to be characteristic of malignant tissues in general. These substances will be studied by the subcellular fractionation techniques that we have devised, coupled with specific enzyme analyses and a new tissue culture technique; macromolecular separation, purification and conventional structural analysis; and by immunological techniques. We anticipate that as the result of these studies we will be able to: (a) enhance the tumor-to-nontumor ratio of the test agents, (b) design and produce new tumor-specific lysosomotropic agents that have higher and more specific uptakes in malignant tissues which can in turn be used in radioisotopically labeled forms as tumor-localizing agents in humans for the detection of cancer; and (c) that we will confirm the presence of, separate and identify a Ga67 binding agent that appears to be present in the plasma of animals with malignancies for use as a possible cancer screening agent in humans. We anticipate that this study will result in the design and production of radiopharmaceutical agents for cancer localization as an aid to the treatment of such processes. Improving the cure of human cancer is dependent to a large extent on early diagnosis. Effective treatment requires knowing the extent of the disease and attacking the lesion while it is still localized.